Patent GB-1492768-A (GB)
Title: Piperidyl and tetrahydropyridyl substituted benzothiophenes and processes for the production thereof
IPC: C07D295/08
Filed: 1974-12-04
Abstract: 1492768 2- or 3-(Piperidyl or tetrahydropyridyl)-benzothiophenes CIBA-GEIGY AG 4 Dec 1974 [6 Dec 1973 30 Aug 1974] 52465/74 Heading C2C Novel compounds I wherein Ph is unsubstituted or substituted ophenylene, one of the radicals R 1  and R 2  is hydrogen or C 1-7  alkyl, and the other is piperidyl which is optionally C 1-7  alkylated and is optionally substituted on its N-atom by an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic hydrocarbon radical, which radical is optionally substituted on C-atoms not attached to the N-atom by hydroxy, oxo or C 1-7  alkoxy, and if the piperidyl radical is substituted at its N-atom as defined it may also contain a C-C-double bond emanating from the ring-C- atom bound to the benzo[b]thienyl radical, and acid addition salts thereof are prepared by (a) in a compound II which corresponds to compound I except that it carries on its piperidyl radical R 1  or R 2  no double bond but hydroxy on the ring-C-atom bound to the benzo[b]thienyl radical, and carries a substituent as defined on the N-atom, water is split off to form a compound I in which the piperidyl radical contains a double bond; (b) in a compound III which corresponds to compound I except that it carries an acyl radical on the N-atom of the piperidyl R 1  or R 2  which may be C-lower alkylated but does not contain a double bond emanating from the ring-C-atom bound to the benzo[b]thienyl radical, the N-acyl radical is split off by solvolysis, to form a compound I in which the N-atom of the piperidyl is unsubstituted; (c) in a compound I having a C-C- double bond in its piperidyl radical R 1  or R 2  or in a corresponding compound IV which carries no substituent on the N-atom of its piperidyl radical R 1  or R 2 , the C-C-double bond in the piperidyl radical is hydrogenated; to form a compound I is which the piperidyl radical contains no double bond; (d) in a compound I having no double bond in its piperidyl radical R 1  or R 2  but an α-arylalkyl radical on the piperidyl-N-atom the α-arylalkyl radical is split off by hydrogenolysis to form a compound I; (e) a compound I carrying no substituent on its piperidyl-N-atom and accordingly no double bond in its piperidyl radical, or a corresponding compound V containing a double bond in its piperidyl radical, is reacted with a reactive ester of an alcohol of Formula VI: HO-R<SP>a</SP> 3  wherein R<SP>a</SP> 3  represents an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic hydrocarbon radical optionally substituted on C-atoms not attached to the nitrogen atom by hydroxy, oxo or lower alkoxy, or a compound I carrying no substituent on its piperidyl-N-atom or a corresponding compound V is reacted, under reducing conditions, with an oxo compound of Formula VII, O = R<SP>b</SP> 3  wherein R<SP>b</SP> 3  represents a geminally bivalent aliphatic, cycloaliphatic, cycloaliphatic - aliphatic or araliphatic hydrocarbon radical, or a compound I carrying no substituent on its piperidyl-N-atom or a corresponding compound V is caused to undergo an addition reaction with a compound of Formula VIII:  wherein R<SP>c</SP> 3  represents an aliphatic, cycloaliphatic, araliphatic or aromatic hydrocarbon radical; or (f) in a compound I which contains bromine as substituent of Ph and a substituent on the piperidyl-N-atom which carries neither hydroxy nor oxo radicals, the bromine atom is converted into the magnesium bromide group, and the resulting Grignard compound is reacted with an oxo-lower-alkane or with a cycloalkanone having 5-10 C-atoms, of which 5-8 are ring-C-atoms to form a compound I correspondingly substituted in the phenyl ring and, optionally, a compound I obtained by one of or by a sequence of the processes given under (a) to (f) is converted into an addition salt with an inorganic or organic acid, or the compound I is liberated from an acid addition salt initially obtained, and/or a compound I present as racemate is split up into its optical antipodes. Compounds I prepared are those in which Ph is unsubstituted, one of R 1  and R 2  is hydrogen or methyl and the other is 1-methyl-1,2,3,6- tetrahydropyridin - 4 - yl, piperidin - 4 - yl, N - methyl, propargyl or 3 - oxo - butyl piperidin - 4 - yl, 1,3 - dimethyl - 1,2,3,6- tetrahydropyridin - 4 - yl or 1,3 - dimethylpiperidin-4-yl. Compounds II are prepared by reacting a compound IX wherein Ph has the meaning given under Formula I, one of the radicals X 1  and X 2  is hydrogen or C 1-7  alkyl and the other is a metal radical, is reacted with a compound of Formula X, O = Pip<SP>a</SP>, wherein Pip<SP>a</SP> is optionally C 1-7  alkylated C-piperidylidene which carries on the N-atom an aliphatic, cycloaliphatic, cycloaliphatic - aliphatic or araliphatic hydrocarbon radical, which radical is optionally substituted on C-atoms not attached to the N- atom by C 1-7  alkoxy. Compounds I inhibit monoamino oxidase the adsorption of nor-adrenaline and serotonin and potentiate the action of 5-hydroxytryptamine and those where R 1  is hydrogen or C 1-7  alkyl have anti-psychotic action. They form with a carrier a pharmaceutical composition which may be administered orally or parenterally.